rs886059160

Variant names:

• chr4-154744140-C-T
• rs886059160
• NM_004744.5:c.-84C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004744.5(LRAT):​c.-84C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 629,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: LRAT NM_004744.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:3
• Conservation: PhyloP100: 0.0910
• Publications: 0 publications found

Genes affected

LRAT (HGNC:6685): (lecithin retinol acyltransferase) The protein encoded by this gene localizes to the endoplasmic reticulum, where it catalyzes the esterification of all-trans-retinol into all-trans-retinyl ester. This reaction is an important step in vitamin A metabolism in the visual system. Mutations in this gene have been associated with early-onset severe retinal dystrophy and Leber congenital amaurosis 14. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

LRAT Gene-Disease associations (from GenCC):

• Leber congenital amaurosis 14

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• severe early-childhood-onset retinal dystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004744.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRAT	NM_004744.5	MANE Select	c.-84C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_004735.2
	LRAT	NM_004744.5	MANE Select	c.-84C>T		5_prime_UTR	Exon 1 of 3	NP_004735.2
	LRAT	NM_001301645.2		c.-1-186C>T		intron	N/A	NP_001288574.1	O95237

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRAT	ENST00000336356.4	TSL:1 MANE Select	c.-84C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000337224.3	O95237
	LRAT	ENST00000336356.4	TSL:1 MANE Select	c.-84C>T		5_prime_UTR	Exon 1 of 3	ENSP00000337224.3	O95237
	LRAT	ENST00000507827.5	TSL:1	c.-1-186C>T		intron	N/A	ENSP00000426761.1	O95237

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152178 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000105 AC: 5 AN: 477712 Hom.: 0 Cov.: 5 AF XY: 0.0000119 AC XY: 3 AN XY: 253060

African (AFR) AF: 0.00 AC: 0 AN: 13446

American (AMR) AF: 0.0000854 AC: 2 AN: 23410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14558

East Asian (EAS) AF: 0.00 AC: 0 AN: 31216

South Asian (SAS) AF: 0.00 AC: 0 AN: 48866

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2028

European-Non Finnish (NFE) AF: 0.0000104 AC: 3 AN: 287430

Other (OTH) AF: 0.00 AC: 0 AN: 27072

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152178 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74332

African (AFR) AF: 0.0000724 AC: 3 AN: 41458

American (AMR) AF: 0.000196 AC: 3 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Leber congenital amaurosis 14 (1)
-	1	-	Retinal dystrophy (1)
-	1	-	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.85
PhyloP100		0.091
PromoterAI		-0.047	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs886059160; hg19: chr4-155665292;